Southern Japan and the Carribean are both endemic for human T-lymphotropic virus type I (HTLV-I) infection. In these areas, however, epidemiology of HTLV-I appears to differ. Various observations from population-based studies indicate that differences in host immune response to virus infection is likely to result in different disease manifestations across geographic regions. While gender, age and route of infection may partly determine host immune response, the observed geographic differences may also reflect, in part, host genetic background as evidenced by the distribution of human leukocyte antigens (HLA) and other polymorphic genes in addition to the presence of environmental factors. The natural history of HTLV-I in southern Japan has been investigated in the population-based Miyazaki Cohort Study, in which approximately 500 HTLV-I positive and 1,500 HTLV-I negative subjects, primarily aged 40 or older, have been prospectively followed for nearly 15 years. While this cohort has provided a wealth of data on sexual transmission, disease pathogenesis and gender effect, the lack of data on younger individuals and clinically diagnosed HTLV-I-associated diseases other than adult T-cell leukemia (ATL) has been a major limitation. In contrast, NCIs on-going follow-up study of HTLV-I carriers in Jamaica, Mother-Infant Cohort (JMI) Study, which currently follows approximately 150 women and their children over 10 year period, has yielded critical information on perinatal transmission and disease pathogenesis among children and younger women. However, by design, this study serves limited purposes for examining gender effect and the incidence of HTLV-I associated diseases among older age groups.Notable differences in incidence and prevalence of HTLV-I associated diseases in adults and children reported across geographic regions underscore the need for comparative studies in these endemic areas. In addition, analyses of larger, pooled data of HTLV-I carriers from different geographic areas are needed to ensure statistical power in studies of gene-environment interactions with extended use of molecular markers. To that goal, we plan to conduct a new prospective cohort study of blood donors in Jamaica, which enrolls a comparable number of HTLV-I positive and HTLV-I negative persons as the Japanese cohort. We will address selected hypotheses regarding HTLV-I transmission and pathogenesis that are outstanding from previous investigations.